| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
We examined the mechanism of Mn-SOD mRNA induction by inflammatory cytokines using primary rat hepatocytes and cultured human hepatoma cell line (Huh-6). Among inflammatory cytokines, Interleukin-1 (IL-1) induced the expression of Mn-SOD mRNA both in primary rat hepatocytes and Huh-6. Actinomycin D,an inhibitor of transcription, did not affect the IL-1-mediated induction of Mn-SOD mRNA.Cycloheximide, an inhibitor of protein synthesis, inhibited the IL-1-mediated induction of Mn-SOD mRNA.These results suggest that the increased expression of Mn-SOD mRNA is controlled at the transcriptional level and that it is due to synthesis of new protein. We examine the IL-1-mediated signal pathways leading to the induction of Mn-SOD mRNA using Huh-6. Phosphatidylcholine-phospholipase C might be a candidate responsible for the signal pathways. We next examined the DNA bindingactivity of C/EBP and NFkB after addition of IL-1 into the cultured medium.The activity of C/EBP did not change, but the activity of NFkB increased. TPCK,an inhibitor of NFkB,decreased the induction of Mn-SOD mRNA expression by IL-1.Furthermore, IL-1 enhanced the expression of p65 mRNA,which constitutes NFkB.We concluded that NFkB is essential for the increased expression of IL-1-mediated Mn-SOD mRNA.
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